In recent years, cancer therapy has witnessed the successful development and clinical implementation of a wide array of tools to fight cancer, including, for example, monoclonal antibodies and adoptive cell therapies (ACT). Immunotherapies employing such tools to reinvigorate T-cells continue to change patient care by providing durable benefit in patients with advanced solid tumors. The latter is offset, however, by a large share of patients that present little response to immunotherapy, in part due to T-cell dysfunction. To overcome this issue, we constructed a chimeric oncolytic adenovirus (TILT-123; Ad5/3-E2F-D24-TNFa-IRES-IL2) capable of expressing tumor necrosis factor alpha (TNFa) and interleukin-2 (IL-2). The use of this agent in preclinical cancer models led to complete responses and favorable immunological effects, both as monotherapy or, in combination with immune checkpoint inhibitors and ACT using tumor-infiltrating lymphocytes (TIL) or chimeric antigen receptor T-cells.
Blood from patients enrolled in TILT-T115, a clinical study using TILT-123 as monotherapy in patients with injectable advanced solid tumors (NCT04695327), was collected at screening and during treatment, and peripheral blood mononuclear cells (PBMCs) and serum were extracted. Immunological effects were evaluated by detecting immune cell populations in PBMCs by flow cytometry, and by detecting cytokines in blood serum by a targeted multiplexed immuno-assay.
Preliminary immunological data points at immune effects both in PBMCs and blood serum of patients undergoing treatment. Immunological data (e.g. flow cytometry and/or cytokine data) will be presented.
TILT-123 can induce systemic immunological effects supporting the continued development of the agent as cancer immunotherapy.
NCT04695327 (first posted January 5, 2021).
TILT Biotherapeutics Ltd.
TILT Biotherapeutics Ltd.
J.M. Santos, V. Cervera-Carrascon, C. Kistler: Financial Interests, Institutional, Full or part-time Employment: TILT Biotherapeutics Ltd; Financial Interests, Personal, Stocks/Shares: TILT Biotherapeutics Ltd. S. Sorsa: Financial Interests, Personal, Stocks/Shares: TILT Biotherapeutics Ltd; Financial Interests, Institutional, Full or part-time Employment: TILT Biotherapeutics Ltd. R. Havunen: Financial Interests, Institutional, Full or part-time Employment: TILT Biotherapeutics Ltd. A. Hemminki: Financial Interests, Personal, Stocks/Shares: Targovax, TILT Biotherapeutics Ltd; Financial Interests, Institutional, Full or part-time Employment, CEO: TILT Biotherapeutics Ltd; Financial Interests, Institutional, Member of the Board of Directors: TILT Biotherapeutics Ltd. All other authors have declared no conflicts of interest.